The objective is to combine basic investigations in nutrition with their application to clinical medicine, especially the nutritional anemias. The research is aimed particularly at developing methodology and techniques, including improved assays for substances of biological importance (including the various physiologic binders for B 12 and folate). It is believed such methodology will provide more accurate tools for diagnosis and differential diagnosis of derangements of nutrition due not only to inadequate ingestion, but also to deranged absorption, transport, utilization, requirements, or excretion. The studies also aim to help delineate total daily requirements for nutrients, particularly vitamine B12 and folic acid, including in "total requirement" the minimal daily requirement from exogenous sources (i.e., food), that part of the daily requirement met by reabsorption of nutrients excreted in bile, and factors adversely affecting or enhancing availability and absorption of nutrients. The studies also are aimed at developing laboratory methods for predicting the therapeutic value and appropriate dosage to avoid toxicity of a wide variety of agents which directly or indirectly interfere with nutrient metabolism. These laboratory methods will employ various in vitro human cell systems, both normal and malignant (including cultures of bone marrow cells, tumor cells, lymphocytes, monocytes, granulocytes, epithelial cells, and others). Our studies so far suggest that with these laboratory tools we can take a given potential chemotherapeutic agent and, before it is given to a human, predict in the test tube whether it will be more damaging to the patient or to his disease, and to what degree. We have also become involved in investigations of selective nutrient deficiency involving one cell line but not another in the same patient, and will be pursuing this fascinating new area further.